Vagal Nerve Stimulation for Multiple Sclerosis

(VANISH-MS Trial)

Overseen By Shayna Pehel

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: NYU Langone Health

Must be taking: High efficacy DMT

Must not be taking: Beta-blockers, Calcium channel blockers, SP1 inhibitors

Disqualifiers: Stroke, Parkinson's, Diabetes, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 20

Duration: 4 weeks

30 Participants Needed

Trial Summary

What is the purpose of this trial?

Growing evidence suggests that vagal nerve stimulation (VNS) may be novel and effective in the management of the symptom burden of multiple sclerosis (MS) potentially by reducing inflammation and emotional distress, therefore improving overall well-being. We will complete a pilot study comparing transcutaneous auricular vagus nerve stimulation (taVNS) and transcutaneous cervical vagus nerve stimulation (tcVNS) to a standard intervention of dorsolateral prefrontal cortex (DLPFC) transcranial direct current stimulation (tDCS) as an active control. The primary outcome will be feasibility and the preliminary efficacy data concerning self-reported symptom reduction to inform the design of an intervention, and estimated power needed to complete a larger sham-controlled RCT. We will also measure heart rate variability (HRV), an easily obtained biomarker of vagus nerve stimulation (VNS), in correspondence to intervention response.

Will I have to stop taking my current medications?

The trial requires that you do not use certain medications that can affect heart rate variability, such as beta-blockers, calcium channel blockers, cardiac glycosides, and SP1 inhibitors like Fingolimod, Siponimod, Ozanimod, and Ponesimod.

What data supports the effectiveness of the treatment Vagal Nerve Stimulation for Multiple Sclerosis?

Research shows that non-invasive vagus nerve stimulation (VNS) has been effective in treating conditions like epilepsy, depression, and headaches. This suggests potential benefits for other neurological conditions, such as multiple sclerosis, by improving autonomic balance and function. ^{1 2 3 4 5}

Is vagal nerve stimulation safe for humans?

Vagal nerve stimulation, especially the non-invasive transcutaneous auricular vagus nerve stimulation (taVNS), is generally considered safe for humans. Most studies report only mild and temporary side effects like ear pain, headache, and tingling, with no severe adverse events linked to taVNS. ^{2 5 6 7 8}

How does the treatment Vagal Nerve Stimulation for Multiple Sclerosis differ from other treatments for this condition?

This treatment is unique because it uses a non-invasive method to stimulate the vagus nerve through the skin, either at the ear or neck, without surgery. It is less expensive and more accessible compared to traditional invasive methods, and it may help improve symptoms like tremors and swallowing difficulties in multiple sclerosis by modulating brain and immune functions. ^{1 2 3 4 9}

Research Team

Leigh Charvet, PhD

Principal Investigator

NYU Langone Health

Eligibility Criteria

This trial is for individuals with multiple sclerosis (MS) who are interested in a non-drug approach to manage their symptoms. Participants should be willing to undergo novel nerve stimulation treatments remotely and have the ability to report on symptom changes.

Inclusion Criteria

I can complete daily tasks with little to no help.

I am between 25 and 65 years old.

SymptoMScreen Score ≥12

Exclusion Criteria

I have had surgery on my vagus nerve.

Nicotine use in the past 6 months (smoking/vaping)

I have been diagnosed with POTS.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either taVNS, tcVNS, or tDCS for symptom management in MS

4 weeks

20 daily sessions

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Remotely Supervised Transcranial Direct Current Stimulation (RS - tDCS)
• Remotely Supervised Transcutaneous Auricular Vagus Nerve Stimulation (RS - taVNS)
• Remotely Supervised Transcutaneous Cervical Vagus Nerve Stimulation (RS - tcVNS)

Trial Overview The study tests two types of vagal nerve stimulation: one applied at the ear (taVNS) and another at the neck (tcVNS), against a control method using brain stimulation (tDCS). The goal is to see which method is more feasible and effective in reducing MS symptoms.

Participant Groups

Group I: Active tcVNS Experimental Treatment 1 Intervention

20 daily 20-minute sessions of active tcVNS.

Group II: Active taVNS Experimental Treatment 1 Intervention

20 daily 60-minute sessions of active taVNS.

Group III: Active DLPFC tDCS Active Control 1 Intervention

20 daily 20-minute sessions of active tDCS.

Who Is Running the Clinical Trial?

NYU Langone Health

Lead Sponsor

Trials

1,431

Recruited

838,000+

Findings from Research

Transcutaneous vagus nerve stimulation (tVNS) is a non-invasive and less expensive alternative to invasive vagus nerve stimulation (VNS), which is used to treat conditions like epilepsy and depression, but requires further research to optimize stimulation sites and parameters.

tVNS has the potential to activate various brain areas and may be effective for a wide range of conditions, including medication-refractory epilepsy, depression, migraines, and more, suggesting it could become a standard treatment for enhancing autonomic function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous vagus nerve stimulation - A brief introduction and overview. Hilz, MJ.[2022]

Transcutaneous auricular vagus nerve stimulation (taVNS) is a non-invasive and cost-effective method for modulating the vagus nerve, making it a promising alternative to traditional surgical vagus nerve stimulation.

taVNS allows for easy and safe administration, with considerations for proper electrode placement and individual dosing based on perception thresholds, which enhances its potential for treating various central and peripheral diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Laboratory Administration of Transcutaneous Auricular Vagus Nerve Stimulation (taVNS): Technique, Targeting, and Considerations. Badran, BW., Yu, AB., Adair, D., et al.[2020]

Cervical vagus nerve stimulation (VNS) can potentially treat various disorders, and this study developed models to estimate the engagement of different nerve fiber types (A, B, and C fibers) based on physiological responses like EMG, heart rate, and breathing intervals in anesthetized rats.

The findings suggest that specific physiological markers correlate with the activation of different fiber types, which could allow for noninvasive monitoring of VNS therapy in humans, enhancing the precision of treatment calibration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quantitative estimation of nerve fiber engagement by vagus nerve stimulation using physiological markers. Chang, YC., Cracchiolo, M., Ahmed, U., et al.[2021]

Vagus nerve stimulation (VNS) is an FDA-approved treatment for conditions like drug-refractory epilepsy and treatment-refractory major depressive disorders, working by influencing both the brain and internal organs through its effects on the autonomic and neuroendocrine systems.

VNS operates via the cholinergic anti-inflammatory pathway, which helps regulate immune responses and reduce inflammation, highlighting its potential for treating a variety of neuropsychiatric and systemic diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neuroimmunomodulation of vagus nerve stimulation and the therapeutic implications. Fang, YT., Lin, YT., Tseng, WL., et al.[2023]

Vagus nerve stimulation (VNS) is effective for treating refractory epilepsy and depression, but traditional methods involve surgical implantation, which carries risks such as infection and bradycardia.

New non-invasive VNS systems eliminate the need for surgery, improving safety and tolerability, and allowing patients to administer stimulation on demand, potentially expanding its use in various medical conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Surgically implanted and non-invasive vagus nerve stimulation: a review of efficacy, safety and tolerability. Ben-Menachem, E., Revesz, D., Simon, BJ., et al.[2022]

The study demonstrated that remote supervised administration of transcutaneous auricular vagus nerve stimulation (taVNS) at home is feasible for 12 patients with autism spectrum disorder (ASD), achieving an 88.5% completion rate over 132 sessions.

Initial results indicated improvements in anxiety and sleep measures after 2 weeks of treatment, suggesting potential efficacy that warrants further investigation in larger trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Remotely supervised at-home delivery of taVNS for autism spectrum disorder: feasibility and initial efficacy. Black, B., Hunter, S., Cottrell, H., et al.[2023]

Transcutaneous auricular vagus nerve stimulation (taVNS) is generally safe, with a low incidence of mild and transient adverse effects, such as ear pain, headache, and tingling, reported in only 24.86% of the studies analyzed.

In a systematic review of 177 studies involving 6322 subjects, there was no significant difference in the risk of adverse events between taVNS and control groups, indicating that taVNS is a feasible option for clinical intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of transcutaneous auricular vagus nerve stimulation (taVNS): a systematic review and meta-analysis. Kim, AY., Marduy, A., de Melo, PS., et al.[2023]

Transcutaneous auricular vagus nerve stimulation (taVNS) is a safe and effective neuromodulation therapy for a variety of conditions, including epilepsy, depression, and anxiety, indicating its broad therapeutic potential.

Despite its effectiveness, there is currently no standardization among taVNS devices, and further research is needed to clarify the relationship between stimulation parameters and therapeutic outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous auricular vagus nerve stimulators: a review of past, present, and future devices. Wang, L., Wang, Y., Wang, Y., et al.[2022]

Vagus nerve stimulation (VNS) showed promising results in improving postural cerebellar tremor and dysphagia in three patients with multiple sclerosis over a period of two to three months.

The improvements are likely linked to VNS's effect on the nucleus tractus solitarius, which plays a role in controlling swallowing and motor functions, suggesting VNS could be a novel treatment option for severe MS symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vagal nerve stimulation improves cerebellar tremor and dysphagia in multiple sclerosis. Marrosu, F., Maleci, A., Cocco, E., et al.[2007]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Transcutaneous vagus nerve stimulation - A brief introduction and overview. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Laboratory Administration of Transcutaneous Auricular Vagus Nerve Stimulation (taVNS): Technique, Targeting, and Considerations. [2020]

3. United States pubmed.ncbi.nlm.nih.gov

Quantitative estimation of nerve fiber engagement by vagus nerve stimulation using physiological markers. [2021]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Neuroimmunomodulation of vagus nerve stimulation and the therapeutic implications. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Surgically implanted and non-invasive vagus nerve stimulation: a review of efficacy, safety and tolerability. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Remotely supervised at-home delivery of taVNS for autism spectrum disorder: feasibility and initial efficacy. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Safety of transcutaneous auricular vagus nerve stimulation (taVNS): a systematic review and meta-analysis. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Transcutaneous auricular vagus nerve stimulators: a review of past, present, and future devices. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Vagal nerve stimulation improves cerebellar tremor and dysphagia in multiple sclerosis. [2007]